Escolar Documentos
Profissional Documentos
Cultura Documentos
National Cancer Act for War on Cancer passed in 1971 Each day, 1,500 Americans die from cancer More than 40% of men and 33% of women at risk for cancer in their lifetimes
WHO projects 15 million cases / year in 2020 Up to 2/3rd s of cancers may be avoidable or preventable (Doll & Peto)
Personal changes in diet, lifestyle, habits Environmental interventions Control and vaccination for infection (hepB, h. pylori, papillomavirus)
normal cell
DNA Interaction
preneoplastic
malignant
PROGRESSION
PROMOTION INITIATION
Complementary Medicines
WHO estimates that 80% of world population relies on plant-based medicines for primary healthcare 75% of all pharmaceuticals were discovered by examining use of plants in traditional medicine
Hope or Hype?
Alternative medicine is edging into the mainstream, with Californians leading the way. The appeal is complex, and debate rages about its effectiveness and scientific oversight
Alternative Therapies
Complementary Therapies with Potential Benefit in Cancer Prevention or Therapy: Ongoing Clinical Trials
Saw Palmetto: BPH, prostate cancer? Lycopene: prostate cancer Beta-Glucans: lymphoma, activate complement receptor-3 to promote antitumor immunity Squalamine: non-small cell lung cancer, ovarian cancer Scutelleria: prostate, breast cancers Green tea: breast cancer, prostate cancer, oral cancers
Herbal Therapies
Herbal supplements not standardized for safety, purity,efficacy Standardized ginseng has defined % ginsenosides, but more than 30 ginsenosides may contribute to biologic effect; different suppliers provide different amounts Natural not necessarily beneficial Drug effects (PC-SPES reduces PSA prostate CA but decreases libido, breast enlarge, nausea, diarrhea, thromboembolism) Unknown drug interactions
Toxic metals lead, cadmium, mercury, arsenic Pesticides Microbes Toxins Botanicals chlorinated pesticide, organic phosphate, triazin herbicide, fungicide, carbamate insecticides Staphylococcus aureus, E. coli, salmonella, shigella, Pseudomonas aeruginosa aflatoxin, bacterial endotoxins digitalis, rauwolfia, belladonna alkaloids
Wood (2002) NEJM 347 : 2046
breast yam milk thistle kava kava prost cod liver oil
Hepatotoxicity
Renal toxicity
Neurotoxicity
Lung Cancer The leading cause of cancer mortality in men and women
Age-adjusted death rates for lung cancer and breast cancer among women, US, 1930-1997 (Patel et al. JAMA 291 : 1763, 2004)
TumorAssociated Angiogenesis
SQUALAMINE
Blocks blood vessel growth in tumors H3C Starves tumors
H3N
+
O O S O O CH3 CH3
H3C H3C
+ +
N H
2
N H
2
OH
Natural steroid, now synthesized in laboratory Recent orphan drug designation by FDA
Squalamine blocks vascular growth factor (VEGF)-induced reorganization and growth of tumor-associated endothelial cells
CON
SQ
VEGF
VEGF + SQ
2000
1000
Preparation of Extracts from Chinese Herbs for Preclinical Testing More than 120 herbs reported to have breast selectivity in TCM practice
Preparation of selected herbal extracts (UCLAs CDSRB)
Campbell et al. (2002)
Herb, Scutellaria baicalcinosis, blocks activation of MAP Kinase by growth factors and estrogen in human breast cancer cells
CON GF GF/HE
80 70 60 50 40 30 20 10 0 0 10 20
MCF-7/HER-2
MCF-7 Parent
30
40
50
60
70
80
90 100
25
30
Figure 3.
Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10,998 vegetarians and non-vegetarians in the United Kingdom
In a cohort of 10,998 men and women, 95 incident cases of colorectal cancer were recorded after 17 years. Risk increased in association with smoking, alcohol, and white bread consumption, and decreased with frequent consumption of fruit. The relative risk in vegetarians compared with nonvegetarians was 0.85 (95% CI)
British Journal of Cancer (2004)
Chemoprevention Initiatives
People eating 5 servings/day friuts & veggies have 1/2 risk of developing cancer of those who eat < 2 servings/ day NCI identified 35 plant-based foods with cancerpreventive activity : garlic, soybean, ginger, onion, tumeric, tomatoe and cruciferous vegetables NCI Five-A-Day for Better Health Program encourages eating fruits & veg 5 servings/day European Prospective Investigation of Cancer & Nutrition (EPIC) - enrolled 520,000 subjects to identify dietary determinants of cancer
Nutragenomics
Herbal and natural product compounds disrupt molecular signaling pathways in precancerous and cancer cells Specific genes may contribute to individual differences in susceptibility to cancer With identification of high risk groups in the future, specific dietary supplements may restore normal cell signaling events Designer foods and natural products
Recommendations
Obtain most your nutrients and phytochemicals from foods rather than supplements Eat in moderation from a variety of food groups, especially fruits and vegetables (5 per day) Favor dishes with multi-plant based ingredients: salads, soups; add leafy greens to sandwiches Maintain a healthy weight DO NOT SMOKE
The Promise of New Antitumor Products Valuable plants and natural products may be lost before their medical use can be discovered
SMOG
Asbestos
Dioxin
A Toxic Landscape
Dozens of toxic chemicals indoors in American homes Study of 120 residential homes in Massachusetts showed 67 carcinogenic chemicals in nail polish, hair-spray, some detergents, household cleaners, pesticides DDT, banned in US 30 years ago, found in dust of 65% of homes
Environmental Science & Technol, 2003
Acknowledgements
Stiles Fund Dr. Michael Tobias Jane Morrison JCCC/UCLA Diana Marquez Hsiao-Wang Chen Rebecca Rausch Cary Freeny Wells Fargo Foundation David Heber Steve Dubinett California BCRP Judith Gasson Lonnie Zeltzer US Army OCRP Dennis Slamon